Cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) are molecules produced by a variety of cells, such as monocytes and macrophages, which have been identified as mediators of inflammatory processes. Cytokines, including TNF, regulate the intensity and duration of the inflammatory response which occurs as the result of an injury or infection. Elevated levels of TNF play an important role in pathologic inflammation. TNF also referred to as (TNFα) has been implicated in the pathophysiology of a variety of human diseases and disorders, including sepsis, infections, autoimmune diseases, transplant rejection and graft-versus-host disease (see e.g., Moeller et al. (1990) Cytokine 2: 162; U.S. Pat. No. 5,231,024 to Moeller et al.; European Patent Publication No. 260 610 BI by Moeller, A. et al.; Vasilli (1992) Annu. Rev. Immunol. 10: 411; Tracey and Cerami (1994) Annu. Rev. Med. 45:491).
TNF has been implicated in psoriasis. Expression of TNF-induced proteins and the presence of activated T lymphocytes in psoriatic plaques but not uninvolved skin, suggest their involvement in the pathogenesis of the disease. There are several types of psoriasis according to cutaneous manifestations: plaque psoriasis, guttate psoriasis, erythrodermic psoriasis, generalized pustular and localized pustular psoriasis. Plaque psoriasis is the most common type, however. Treatment of psoriasis depends on the extent of the disease. Topical corticosteroids are commonly used for mild to moderate localized cases. Keratolytic agents and coal tar are also used as topical medications, and phototherapy is commonly used for more widespread disease. Other systemic therapy, such as methotrexate cyclosporine and synthetic retinoids are effective, but are often administered in rotation due to their possible cumulative toxic effect.
TNF has also been implicated in Crohn's disease. Crohn's is diagnosed on the basis of clinical, endoscopic, radiographic, and histologic criteria. The treatment of Crohn's disease is challenging. Treatment is based on location, extent, and severity of disease. Current compounds and regimens do not completely abate the inflammatory process and have significant side effects.
The goal of medical treatment for Crohn's disease includes improving patients' quality of life while reducing the need for hospitalization and surgery. The current medical armamentarium includes 5-aminosalicylates, corticosteroids, immunomodulators, and biologic agents, such as anti-TNFα treatments including infliximab (disclosed in EP0610201), etanercept (disclosed in U.S. Pat. No. 8,722,631) and adalimumab (disclosed in WO2005110452). In the prior art, response to treatment has been measured by clinical improvement in symptoms; however, achieving mucosal healing is more challenging. Mucosal healing, or endoscopic remission, is associated with increased rates of clinical remission, fewer hospitalizations, and fewer abdominal surgeries.
It is known to treat TNFα-related disorders with a liquid formulation containing 50 mg/ml Humira® (adalimumab). Of this formulation, 0.8 ml is subcutaneously injected into a subject such that a dose of 40 mg adalimumab is delivered. In order to deliver a higher dose of adalimumab, the subject must receive multiple subcutaneous injections. Thus, there is a need in the art for an improved adalimumab treatment regimen to treat TNFα-related disorders which includes a reduced number of subcutaneous injections to be delivered to a subject as compared to a prior art treatment with adalimumab.